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Degeneration of basal and limbic networks is a core feature of behavioural variant frontotemporal dementia

Vesna Vuksanovic Orcid Logo, Roger T Staff, Suzannah Morson, Trevor Ahearn, Luc Bracoud, Alison D Murray, Peter Bentham Orcid Logo, Christopher M Kipps, Charles R Harrington Orcid Logo, Claude M Wischik

Brain Communications, Volume: 3, Issue: 4

Swansea University Author: Vesna Vuksanovic Orcid Logo

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DOI (Published version): 10.1093/braincomms/fcab241

Abstract

The behavioural variant of frontotemporal dementia is a clinical syndrome characterised by changes in behaviour, cognition and functional ability. Although atrophy in frontal and temporal regions would appear to be a defining feature, neuroimaging studies have identified volumetric differences distr...

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Published in: Brain Communications
ISSN: 2632-1297
Published: Oxford University Press (OUP) 2021
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URI: https://cronfa.swan.ac.uk/Record/cronfa56976
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Although atrophy in frontal and temporal regions would appear to be a defining feature, neuroimaging studies have identified volumetric differences distributed across large parts of the cortex, giving rise to a classification into distinct neuroanatomical sub-types. Here, we extended these neuroimaging studies to examine how distributed patterns of cortical atrophy map onto brain network hubs. We used baseline structural magnetic resonance imaging data collected from 213 behavioural variant of frontotemporal dementia patients meeting consensus diagnostic criteria and having definite evidence of frontal and/or temporal lobe atrophy from a global clinical trial conducted in 70 sites in Canada, United States of America, Australia, Asia and Europe. These were compared with data from 244 healthy elderly subjects from a well-characterised cohort study. We have used statistical methods of hierarchical agglomerative clustering of 68 regional cortical and subcortical volumes (34 in each hemisphere) to determine the reproducibility of previously described neuroanatomical subtypes in a global study. We have also attempted to link the structural findings to clinical features defined systematically using well-validated clinical scales (Addenbrooke&#x2019;s Cognitive Examination Revised, the Mini-Mental Status Examination, the Frontotemporal Dementia Rating Scale and the Functional Assessment Questionnaire) and subscales derived from them. Whilst we can confirm that the subtypes are robust, they have limited value in explaining the clinical heterogeneity of the syndrome. We have found that a common pattern of degeneration affecting a small number of subcortical, limbic and frontal nodes within highly connected networks (most previously identified as rich club members or functional binding nodes) is shared by all the anatomical subtypes. Degeneration in these core regions is correlated with cognitive and functional impairment, but less so with behavioural impairment. These findings suggest that degeneration in highly connected basal, limbic and frontal networks is a core feature of the behavioural variant of frontotemporal dementia phenotype irrespective of neuroanatomical and clinical heterogeneity, and may underly the impairment of integration in cognition, function and behaviour responsible for the loss of insight that characterises the syndrome.</abstract><type>Journal Article</type><journal>Brain Communications</journal><volume>3</volume><journalNumber>4</journalNumber><paginationStart/><paginationEnd/><publisher>Oxford University Press (OUP)</publisher><placeOfPublication/><isbnPrint/><isbnElectronic/><issnPrint/><issnElectronic>2632-1297</issnElectronic><keywords>behavioural variant frontotemporal dementia, brain networks, rich club, neurodegeneration, anatomical subtypes</keywords><publishedDay>15</publishedDay><publishedMonth>12</publishedMonth><publishedYear>2021</publishedYear><publishedDate>2021-12-15</publishedDate><doi>10.1093/braincomms/fcab241</doi><url/><notes/><college>COLLEGE NANME</college><department>Health Data Science</department><CollegeCode>COLLEGE CODE</CollegeCode><DepartmentCode>HDAT</DepartmentCode><institution>Swansea University</institution><apcterm/><funders>This study was sponsored entirely by TauRx Therapeutics Ltd (PAR1577). 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spelling 2022-10-27T11:46:17.9791306 v2 56976 2021-05-27 Degeneration of basal and limbic networks is a core feature of behavioural variant frontotemporal dementia a1a6e2bd0b6ee99f648abb6201dea474 0000-0003-4655-698X Vesna Vuksanovic Vesna Vuksanovic true false 2021-05-27 HDAT The behavioural variant of frontotemporal dementia is a clinical syndrome characterised by changes in behaviour, cognition and functional ability. Although atrophy in frontal and temporal regions would appear to be a defining feature, neuroimaging studies have identified volumetric differences distributed across large parts of the cortex, giving rise to a classification into distinct neuroanatomical sub-types. Here, we extended these neuroimaging studies to examine how distributed patterns of cortical atrophy map onto brain network hubs. We used baseline structural magnetic resonance imaging data collected from 213 behavioural variant of frontotemporal dementia patients meeting consensus diagnostic criteria and having definite evidence of frontal and/or temporal lobe atrophy from a global clinical trial conducted in 70 sites in Canada, United States of America, Australia, Asia and Europe. These were compared with data from 244 healthy elderly subjects from a well-characterised cohort study. We have used statistical methods of hierarchical agglomerative clustering of 68 regional cortical and subcortical volumes (34 in each hemisphere) to determine the reproducibility of previously described neuroanatomical subtypes in a global study. We have also attempted to link the structural findings to clinical features defined systematically using well-validated clinical scales (Addenbrooke’s Cognitive Examination Revised, the Mini-Mental Status Examination, the Frontotemporal Dementia Rating Scale and the Functional Assessment Questionnaire) and subscales derived from them. Whilst we can confirm that the subtypes are robust, they have limited value in explaining the clinical heterogeneity of the syndrome. We have found that a common pattern of degeneration affecting a small number of subcortical, limbic and frontal nodes within highly connected networks (most previously identified as rich club members or functional binding nodes) is shared by all the anatomical subtypes. Degeneration in these core regions is correlated with cognitive and functional impairment, but less so with behavioural impairment. These findings suggest that degeneration in highly connected basal, limbic and frontal networks is a core feature of the behavioural variant of frontotemporal dementia phenotype irrespective of neuroanatomical and clinical heterogeneity, and may underly the impairment of integration in cognition, function and behaviour responsible for the loss of insight that characterises the syndrome. Journal Article Brain Communications 3 4 Oxford University Press (OUP) 2632-1297 behavioural variant frontotemporal dementia, brain networks, rich club, neurodegeneration, anatomical subtypes 15 12 2021 2021-12-15 10.1093/braincomms/fcab241 COLLEGE NANME Health Data Science COLLEGE CODE HDAT Swansea University This study was sponsored entirely by TauRx Therapeutics Ltd (PAR1577). The Maxwell Computer Cluster is funded by the University of Aberdeen. 2022-10-27T11:46:17.9791306 2021-05-27T11:31:30.6202254 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine Vesna Vuksanovic 0000-0003-4655-698X 1 Roger T Staff 2 Suzannah Morson 3 Trevor Ahearn 4 Luc Bracoud 5 Alison D Murray 6 Peter Bentham 0000-0002-6443-3353 7 Christopher M Kipps 8 Charles R Harrington 0000-0003-2250-3920 9 Claude M Wischik 10 56976__22010__099556114b7440828dbfe6d835582722.pdf 56976 VoR.pdf 2022-01-04T15:06:37.4340282 Output 1242794 application/pdf Version of Record true The Author(s) (2021). This is an Open Access article distributed under the terms of the Creative Commons Attribution License true eng https://creativecommons.org/licenses/by/4.0/
title Degeneration of basal and limbic networks is a core feature of behavioural variant frontotemporal dementia
spellingShingle Degeneration of basal and limbic networks is a core feature of behavioural variant frontotemporal dementia
Vesna Vuksanovic
title_short Degeneration of basal and limbic networks is a core feature of behavioural variant frontotemporal dementia
title_full Degeneration of basal and limbic networks is a core feature of behavioural variant frontotemporal dementia
title_fullStr Degeneration of basal and limbic networks is a core feature of behavioural variant frontotemporal dementia
title_full_unstemmed Degeneration of basal and limbic networks is a core feature of behavioural variant frontotemporal dementia
title_sort Degeneration of basal and limbic networks is a core feature of behavioural variant frontotemporal dementia
author_id_str_mv a1a6e2bd0b6ee99f648abb6201dea474
author_id_fullname_str_mv a1a6e2bd0b6ee99f648abb6201dea474_***_Vesna Vuksanovic
author Vesna Vuksanovic
author2 Vesna Vuksanovic
Roger T Staff
Suzannah Morson
Trevor Ahearn
Luc Bracoud
Alison D Murray
Peter Bentham
Christopher M Kipps
Charles R Harrington
Claude M Wischik
format Journal article
container_title Brain Communications
container_volume 3
container_issue 4
publishDate 2021
institution Swansea University
issn 2632-1297
doi_str_mv 10.1093/braincomms/fcab241
publisher Oxford University Press (OUP)
college_str Faculty of Medicine, Health and Life Sciences
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hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Medicine{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Medicine
document_store_str 1
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description The behavioural variant of frontotemporal dementia is a clinical syndrome characterised by changes in behaviour, cognition and functional ability. Although atrophy in frontal and temporal regions would appear to be a defining feature, neuroimaging studies have identified volumetric differences distributed across large parts of the cortex, giving rise to a classification into distinct neuroanatomical sub-types. Here, we extended these neuroimaging studies to examine how distributed patterns of cortical atrophy map onto brain network hubs. We used baseline structural magnetic resonance imaging data collected from 213 behavioural variant of frontotemporal dementia patients meeting consensus diagnostic criteria and having definite evidence of frontal and/or temporal lobe atrophy from a global clinical trial conducted in 70 sites in Canada, United States of America, Australia, Asia and Europe. These were compared with data from 244 healthy elderly subjects from a well-characterised cohort study. We have used statistical methods of hierarchical agglomerative clustering of 68 regional cortical and subcortical volumes (34 in each hemisphere) to determine the reproducibility of previously described neuroanatomical subtypes in a global study. We have also attempted to link the structural findings to clinical features defined systematically using well-validated clinical scales (Addenbrooke’s Cognitive Examination Revised, the Mini-Mental Status Examination, the Frontotemporal Dementia Rating Scale and the Functional Assessment Questionnaire) and subscales derived from them. Whilst we can confirm that the subtypes are robust, they have limited value in explaining the clinical heterogeneity of the syndrome. We have found that a common pattern of degeneration affecting a small number of subcortical, limbic and frontal nodes within highly connected networks (most previously identified as rich club members or functional binding nodes) is shared by all the anatomical subtypes. Degeneration in these core regions is correlated with cognitive and functional impairment, but less so with behavioural impairment. These findings suggest that degeneration in highly connected basal, limbic and frontal networks is a core feature of the behavioural variant of frontotemporal dementia phenotype irrespective of neuroanatomical and clinical heterogeneity, and may underly the impairment of integration in cognition, function and behaviour responsible for the loss of insight that characterises the syndrome.
published_date 2021-12-15T04:12:21Z
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